Issue 27, 2021

Experimental and computational studies of the mechanism of iron-catalysed C–H activation/functionalisation with allyl electrophiles

Abstract

Synthetic methods that utilise iron to facilitate C–H bond activation to yield new C–C and C–heteroatom bonds continue to attract significant interest. However, the development of these systems is still hampered by a limited molecular-level understanding of the key iron intermediates and reaction pathways that enable selective product formation. While recent studies have established the mechanism for iron-catalysed C–H arylation from aryl-nucleophiles, the underlying mechanistic pathway of iron-catalysed C–H activation/functionalisation systems which utilise electrophiles to establish C–C and C–heteroatom bonds has not been determined. The present study focuses on an iron-catalysed C–H allylation system, which utilises allyl chlorides as electrophiles to establish a C–allyl bond. Freeze-trapped inorganic spectroscopic methods (57Fe Mössbauer, EPR, and MCD) are combined with correlated reaction studies and kinetic analyses to reveal a unique and rapid reaction pathway by which the allyl electrophile reacts with a C–H activated iron intermediate. Supporting computational analysis defines this novel reaction coordinate as an inner-sphere radical process which features a partial iron–bisphosphine dissociation. Highlighting the role of the bisphosphine in this reaction pathway, a complementary study performed on the reaction of allyl electrophile with an analogous C–H activated intermediate bearing a more rigid bisphosphine ligand exhibits stifled yield and selectivity towards allylated product. An additional spectroscopic analysis of an iron-catalysed C–H amination system, which incorporates N-chloromorpholine as the C–N bond-forming electrophile, reveals a rapid reaction of electrophile with an analogous C–H activated iron intermediate consistent with the inner-sphere radical process defined for the C–H allylation system, demonstrating the prevalence of this novel reaction coordinate in this sub-class of iron-catalysed C–H functionalisation systems. Overall, these results provide a critical mechanistic foundation for the rational design and development of improved systems that are efficient, selective, and useful across a broad range of C–H functionalisations.

Graphical abstract: Experimental and computational studies of the mechanism of iron-catalysed C–H activation/functionalisation with allyl electrophiles

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Mar 2021
Accepted
23 May 2021
First published
17 Jun 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 9398-9407

Experimental and computational studies of the mechanism of iron-catalysed C–H activation/functionalisation with allyl electrophiles

J. C. DeMuth, Z. Song, S. H. Carpenter, T. E. Boddie, A. Radović, T. M. Baker, O. Gutierrez and M. L. Neidig, Chem. Sci., 2021, 12, 9398 DOI: 10.1039/D1SC01661J

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